Dispenser for an adhesive tissue sealant

ABSTRACT

A dispenser in which a dry powder (one component of a two-part adhesive tissue sealant and/or adhesive) is stored in a container (e.g., a carpule) having a septum at one end, an open end opposite the septum, and a movable plug. The powder is retained at the septum end of the container by the movable plug, which is displaced and pushed back as the solvent used for reconstituting the powder is introduced (e.g., through the septum). The second part of the tissue sealant is contained within a second container, also with a movable plug. After the first part is reconstituted, a manifold is fitted which pierces both septums and allows the contents to be dispensed. A dual syringe body supports the containers, and has pistons that enter the open ends to advance the movable plugs. Other embodiments of tissue adhesive and/or sealant dispensers and kits as well as methods of preparing tissue sealants are also described.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is a divisional of application Ser. No.09/524,141, filed on Mar. 10, 2000, now allowed, which is acontinuation-in-part of application Ser. No. 08/956,308, filed on Oct.22, 1997, abandond.

TECHNICAL FIELD

[0002] The invention relates generally to the dispensing of adhesivetissue sealants and other liquid preparations, including those requiringmixing immediately prior to use.

BACKGROUND

[0003] A variety of techniques have been used to bond or seal livingtissue. For example, different types of tissues have been mechanicallybound or sealed with a number of procedures, materials and methodsincluding sutures, staples, tapes and bandages. In some applications,these materials are made of absorbable materials that are intended tobond and/or seal tissue as it heals and then to be absorbed over aperiod of time.

[0004] A recent addition to the techniques that can be used isapplication of an absorbable adhesive sealant composition to bond and/orseal tissue. The adhesive composition is readily formed from a twocomponent mixture that includes a first part of a cross-linking agentand a second part of a protein, preferably a serum protein such asalbumin. When the two parts of the mixture are combined, the mixture isinitially liquid. The combined mixture then cures in vivo on the surfaceof tissue to give a substantive composition that securely bonds to thetissue. Additional details can be found in commonly owned U.S. Pat. No.5,583,114, “ADHESIVE SEALANT COMPOSITION,” to Barrows et al, the entirecontents of which are hereby incorporated by reference.

[0005] Among the limitations on the widespread use of this material arethat the first part, when rehydrated, has a limited shelf life and mustbe dissolved relatively shortly before use. Another limitation is thatthe two parts must be kept strictly separate until dispensed onto thetissue because the reaction time of the forming of the finished sealantis quite fast. These limitations increase the complexity for appropriatedispensing by the medical practitioner to form an effective adhesivetissue sealant on the tissue surface.

[0006] A known approach for dispensing two-part tissue sealants is tosupply the user with a kit consisting of at least two syringes, vialscontaining the components in dry powder form, a syringe body forreceiving and supporting both syringes, and a housing for connecting thetwo syringes to a common nozzle. The user fills the syringes by piercingthe septums on the vials and withdrawing solution into the barrel of thesyringe. If a component is in powder form within a vial, the user firstinjects a solvent and then withdraws the reconstituted solution. Theneedles on the syringes are removed, the syringe barrels and plungersare supported in housing, and the syringe nozzles are received in thehousing.

[0007] Another approach is disclosed in U.S. Pat. No. 4,735,616 to Eibl.Dry powder is stored within both barrels of a dual barrel syringe. Ineach instance, the powder is stored on one side of a sliding plug, andsolvent is stored on the other side. When the user presses down on thesyringe plunger, the plugs slide along the barrels to positions at whichthe barrels each have a bulge that provides a bypass for the solvent toreach the powder.

[0008] In these prior art dispensers, the manifold passages connectingthe two syringes to the common nozzle are typically narrow conduits ofcircular cross section. E.g., U.S. Pat. No. 4,631,055 to Red1.

[0009] Carpules have been used in some syringes; e.g., U.S. Pat. No.3,767,085 to Cannon shows a dual carpule syringe for mixing compositionsused in dentistry.

[0010] A kit for reconstitution and application of Tisseel® fibrinsealant including VH Sealer Protein and Thrombin solutions is currentlyavailable from Baxter Healthcare Corporation's division of Glendale,Calif. The use of this product requires a complicated procedure. As aresult, it is difficult to prepare the fibrin sealant with this kit andit is also difficult to use the applicator. Additionally, the applicatoris said to suffer from clogging problems.

[0011] The Tisseel® kit comprises a first bottle containing freeze-driedthrombin, a second bottle with calcium chloride solution designed toreconstitute the thrombin; a third bottle with sealer proteinconcentrate, and a fourth bottle with fibrinolysis inhibitor solution. AFibrinotherm® Heating and Stirring Device is used to heat and stir thecomponents such as the sealer protein concentrate and the fibrinolysisinhibitor solution. Alternatively, a hot water bath or incubator may beused. This requires components to be heated above room temperature priorto use, further complicating the procedure.

[0012] The packaging of this device also causes problems. Two syringesand at least two (and preferably four) exposed needles are requiredsimply to reconstitute the thrombin and sealer protein concentrate. Fortransfer of the Tisseel® VH solution and the Thrombin Solution to thesterile field in the operating room, the scrub nurse should withdraw thesolutions while the circulating nurse holds the unsterile vials. Thisrequires the coordination of two healthcare workers, one of whichdirects a sharp instrument (needle) toward the other. This is requiredtwice to prepare the applicator of the product.

[0013] The packaging also includes multiple pouches that contribute tothe waste and clutter at the location of medical care.

[0014] Outside the United States, a kit is available for use inpreparing and dispensing the Beriplast® fibrin adhesive. This kitincludes four vials with fibrinogen concentrate in a first vial,aprotinin solution in a second vial, thrombin in a third vial andcalcium chloride solution in a fourth vial. An adapter with dualpiercers is available in some kits which helps place the contents of onevial into another. However, once the two components of the fibrinadhesive are in solution form, the kit nevertheless requires two exposedneedles to transfer the solutions from the mixed vials into the separatesyringes of the delivery device. Since the external portion of the vialsare considered non-sterile (i.e. all four vials are packaged in a box),it is believed that this kit also requires the coordination of twohealthcare workers (one associated with the sterile field, one outside),one of which directs a sharp instrument (needle) toward the other.

SUMMARY OF THE INVENTION

[0015] The present invention provides an improved dispenser suitable forquickly and easily setting up and dispensing multi-part tissue sealantsor other multi-part compositions requiring separation of the componentsuntil just prior to application on the tissue surface.

[0016] In a first aspect, the invention features a dispenser having acontainer (e.g., a carpule) with at least a portion of a first componentof a multi-part tissue sealant and/or adhesive (e.g. a dry powder)having a septum at one end, an open end opposite the septum, and amovable plug. The powder may be retained at the septum end of thecontainer by the movable plug, which is preferably displaced and pushedback as a solvent used for reconstituting the powder is introduced(e.g., through the septum). At least a portion (and preferably all) of asecond component of the tissue sealant (e.g. a liquid) is containedwithin a second container, also with a movable plug. After the firstcomponent is reconstituted, a housing (preferably a manifold) havingpiercers is used to pierce both septums and allow the contents to bedispensed. Preferably, the piercers are placed in a protected positionso as not to expose a user to contact with the piercers. A body supportsthe containers. Pistons are provided to advance the movable plugs.

[0017] Preferred implementations of the first aspect may include one ormore of the following features.

[0018] The first component may be a dry powder of a water-compatible orwater-soluble cross-linking agent.

[0019] The aqueous solution for dissolving the powder may be introducedthrough the first septum (e.g., either via the piercer or via aninjection through the septum by a syringe).

[0020] The movable plug may be positioned in a position in which thespace between the plug and the septum is substantially the minimumnecessary to contain the dry powder, thereby reducing the amount of airin that space and consequently the amount of pressure rise associatedwith injecting liquid through the septum. The movable plug can move awayfrom the septum as liquid is injected to reduce any pressure rise.

[0021] The second component stored in the second carpule may be asolution.

[0022] The second component may be a protein dissolved in an aqueousbuffer and capable of reacting with the solution of the first componentto provide the adhesive tissue sealant.

[0023] The body may comprise a retainer for protecting and/or holdingthe containers.

[0024] In a second aspect, the invention features an improved manifoldfor a two-part dispenser. Two containers (e.g., carpules), each having aseptum at one end, an open end opposite the septum, and a movable plug,are supported in a dual syringe body, which has pistons configured toenter the open ends of the containers to advance the movable plugs. Amanifold has cavities that receive the septum ends of the containers,and a disk supporting a piercer (e.g., hollow needle) is mounted in thebase of each cavity so that the septum of a container is pierced when itis installed in a cavity. Each disk is supported a distance above thebase of a cavity to form a plenum defined by the disk and adjacent wallsof the base of the cavity. Liquid exiting a container travels throughthe lumen of the piercer, then into the adjacent plenum, and then out ofthe plenum along a conduit extending to the nozzle. This arrangement ofdisks each supporting a piercer and forming a plenum provides aneffective, relatively low-cost way of constructing a manifold forconnecting carpule piercers to a common nozzle.

[0025] Preferred implementations of the second aspect may include one ormore of the following features.

[0026] Each disk may be sealed to the surrounding wall of the cavity(e.g., by an clastomeric sealing member on the disk) so that theadjacent plenum is defined by the disk and the base of the cavity.

[0027] The conduit and piercer lumen may each communicate with theplenum at laterally spaced apart locations so that flow from the piercerlumen to the conduit changes direction from a generally longitudinalflow path through the piercer lumen, to a generally lateral direction inthe plenum, and then to a generally longitudinal flow path in theconduit.

[0028] The disk may be supported from the base of the cavity bystandoffs.

[0029] The first container may contain a quantity of the first componentin the form of a dry powder so that the first component must bedissolved prior to use by introduction of an aqueous solvent.

[0030] The second container may contain a quantity of protein in anaqueous buffer that is capable of reacting with a dissolved firstcomponent to provide an adhesive tissue sealant.

[0031] In a third aspect, the invention features a method for dispensinga component stored in a dispenser in dry powder form and reconstitutedby introduction of a solvent. A carpule is provided with a septum at oneend, an open end opposite the septum end, and a movable plug disposedtherebetween. The dry powder is stored between the septum and themovable plug. Solvent is introduced into the interior of the containerby piercing the septum with a syringe and injecting the solvent into thecarpule. The carpule is installed in a syringe body and manifold, thelatter providing a flow path from the piercer to an outlet nozzle.

[0032] Preferred implementations of the third aspect may include one ormore of the following features.

[0033] Installing the carpule in the syringe body and manifold may occurbefore or after the solvent is injected through the septum.

[0034] The first movable plug may be positioned in a position in whichthe space between the plug and the septum is substantially the minimumnecessary to contain the dry powder, thereby reducing the amount of airin that space and reducing the pressure increase within the carpule whenthe solvent is introduced by piercing the first septum. The movable plugcan move away from the septum as liquid is injected to reduce anypressure rise.

[0035] The dispenser may comprise a second carpule comprising a secondseptum at one end, an open end opposite the second septum, and a secondmovable plug disposed therein, the second carpule containing a secondcomponent, and the syringe body and manifold may be sized and configuredto accept the first and second carpule.

[0036] The second component may be a protein in an aqueous buffer andcapable of reacting with the first component to provide an adhesivetissue sealant.

[0037] The dry powder of the first component may be a water-compatibleor water-soluble cross-linking agent capable of reacting with the secondcomponent to provide the adhesive tissue sealant.

[0038] In another aspect, the present invention comprises a kit havingcomponents useful for preparing and delivering a tissue sealant and/oradhesive having first and second components. The kit comprises a firstcontainer having a septum, at least a portion of the first componentstored therein, and outer portions. The kit includes a second containerhaving at least a portion of the second component therein, a septum, andouter portions. At least one vial with a solvent for at least one of thefirst and second components is also present in the kit. The kit furtherincludes a syringe and needle; and a sterile housing having first andsecond piercers located in protected positions and a portion that issized and shaped to receive the first and second containers.

[0039] In another aspect, the present invention comprises a method ofpreparing a multiple component tissue sealant and/or adhesive just priorto use comprising the steps of providing a first container having aseptum and a dry powder stored therein; providing a second containerhaving a septum and a liquid therein; providing a vial with a solventfor the dry powder therein; providing a syringe and needle; providing ahousing having first and second piercers located in protected positionsand a portion that is sized and shaped to receive the first and secondcontainers; withdrawing the solvent from the vial with the syringe andneedle; placing the solvent in the first container; and installing thefirst and second containers in the housing and piercing the septums ofthe first and second containers with the first and second piercerswithout exposing a user to physical contant with the piercers.

[0040] The invention provides a significantly simpler and easier to usedispenser, one particularly well suited to handling adhesive tissuesealants. It is also simple and relatively inexpensive to manufacture.It delivers excellent performance, and is particularly good at mixingsolutions reconstituted from dry powder.

[0041] Other features and advantages of the invention will be apparentfrom the following description and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0042] FIGS. 1A-1D are side views of elements of a preferred embodimentof the invention;

[0043]FIG. 2 is a side view of the base of the dual syringe body;

[0044]FIG. 3 is a bottom view of the base of FIG. 2;

[0045]FIG. 4 is a cross-sectional view taken along section lines 4-4 inFIG. 3;

[0046]FIG. 5 is a cross-sectional view taken along section lines 5-5 inFIG. 3;

[0047]FIG. 6 is a perspective view of the dual piston;

[0048]FIG. 7 is a side view of the dual piston of FIG. 6;

[0049]FIG. 8 is a side view of the manifold;

[0050]FIG. 9 is a bottom view of the manifold of FIG. 9;

[0051]FIG. 10 is a cross-sectional view taken along section lines 10-10in FIG. 9;

[0052]FIG. 11 is a perspective exploded view of elements of an alternateembodiment of the invention;

[0053]FIG. 12 is a cross-section front view of the assembled alternateembodiment of FIG. 11; and

[0054]FIG. 13 is a perspective exploded view of elements of anadditional alternate embodiment of the invention;

[0055]FIG. 14 is a cross-section front view of the assembled alternateembodiment of FIG. 13;

[0056]FIG. 15 is a version of a kit including the elements illustratedin FIG. 13;

[0057]FIG. 16 is a top view of a minor subassembly of a kit according toone aspect of the present invention;

[0058]FIG. 17 is a top view of a major subassembly for use with theminor subassembly shown in FIG. 16 according to another aspect of thepresent invention;

[0059]FIGS. 18 through 26 illustrate steps in the use of a kit accordingto one aspect of the present invention wherein

[0060]FIG. 18 illustrates a syringe and needle being loaded with asolvent;

[0061]FIG. 19 illustrates the loaded syringe (after being loaded withsolvent in the operation depicted in FIG. 18) being used to fill a firstcontainer with the solvent to dissolve a first component of a tissueadhesive and/or sealant within the first container;

[0062]FIG. 20 illustrates optional additional manual mixing of the firstcomponent of a tissue adhesive and/or sealant within the firstcontainer;

[0063]FIG. 21 illustrates a container being loaded into the housing of atissue adhesive and/or sealant dispenser;

[0064]FIG. 22 shows a dual piston being received in open ends of firstand second containers of the dispenser;

[0065]FIG. 23 illustrates an optional step of expressing air from thedispenser preassembly;

[0066]FIG. 24 illustrates an optional step of cleaning the surface ofthe housing of the dispenser;

[0067]FIG. 25 shows a dispensing tip being attached to the dispenser;and

[0068]FIG. 26 illustrates the assembled dispenser being used to dispensea tissue adhesive and/or sealant composition.

DETAILED DESCRIPTION

[0069] Referring now to FIGS. 1A-1D, side views of an example of theelements of a dispenser kit 20 according to the present invention areillustrated. The dispenser kit 20 includes a first carpule 22, a secondcarpule 24, a dual syringe body 26 adapted to receive and support thefirst and second carpules, a syringe 28, and a manifold (nozzle body)30. First carpule 22 has a first septum 32 at one end of first carpulebody 34, the other end of the first carpule body being an open end 36.There is a first movable plug 38 disposed within the first carpule 22 sothat a quantity of a first component 40 is contained between the firstseptum 32 and the first movable plug. In preferred embodiments, firstcomponent 40 is a quantity of dry powder of a water-compatible orwater-soluble multi-functional cross-linking agent. Conveniently, thefirst carpule body 34 has a ridge 42 near open end 36 to facilitate theretaining of the first carpule within dual syringe body 26.

[0070] First movable plug 38 is positioned so that the space between theplug and the septum is substantially the minimum necessary to containthe dry powder, thereby 15 reducing the amount of air in the spacebetween the plug and septum. Reducing the amount of air entrapped withthe powder has the benefit that when solvent is injected into thecarpule to dissolve the powder there is less rise in pressure within thecarpule, as the plug is able to move away from the septum to reduce anypressure rise. Elevated pressure is undesirable in that it could lead todifficulty when the solvent is injected into the carpule and when thecarpule is later pierced on insertion in the manifold 30. An elevatedpressure could result, once piercing occurs, in immediate flow of thefirst component into the manifold and nozzle.

[0071] Second carpule 24 has a second septum 44 at one end of secondcarpule body 46, the other end of the second carpule body being an openend 48. There is a second movable plug 50 disposed within the secondcarpule 24 so that a quantity of a second component 52 is containedbetween the second septum 44 and the second movable plug. In preferredembodiments, second component 52 is a quantity of protein in an aqueousbuffer.

[0072] Conveniently, the second carpule body 46 has a ridge 56 near openend 48 to facilitate the retaining of the second carpule within dualsyringe 26.

[0073] Preferably, first and second movable plugs 38 and 50 include alubricant. In a preferred embodiment, the lubricant comprises a coatingof silicone. The lubricant facilitates movement of the plugs relative tothe rest of the containers 22 and 24.

[0074] Also preferably, the first and second septums 32 and 44 are fixedto the containers (e.g. carpules) 22 and 24 by aluminum caps. Theelongate cylindrical portion of the containers 22 and 24 may be glass inone preferred embodiment. The glass allows the user to see the contentsof the containers 22 and 24.

[0075] Dual syringe body 26 includes a base 57 having two cylinders 58and 60 adapted to receive and support the first and second carpules 22and 24. A dual piston 62 is provided, adapted to enter the open ends 36and 48 of the carpules 22 and 24 so as to contact and advance the firstand second movable plugs 38 and 50. A flange 64 is provided to allow thepractitioner to grip the dual syringe body 26 during injection in theconventional manner for syringes. A pair of latches 66 (only one beingvisible in this view) are provided to attach dual syringe body 26 tomanifold 30.

[0076] Syringe 28 is conveniently of conventional type, having a body68, a nozzle or needle 70 at one end, and a piston 72 at the other end.A protective cap 74 is provided to preserve the needle 70 in a sterilecondition until the kit is to be used. The needle 70 is adapted topierce the first septum 32 for injecting the aqueous solvent 76contained within syringe 28 into the first carpule 22. In a preferredembodiment, solvent 76 is pyrogen free sterile water (e.g. USP water forinjection) for dissolving the dry powder of a water-compatible orwatersoluble multi-functional cross-linking agent.

[0077] Manifold 30 is adapted to fit over and pierce the first andsecond septums 32 and 44 after the first component 40 has been mixedwith the solvent 76. Manifold 30 has a dual nozzle 78, which in thepreferred embodiment keeps the first and second components 40 and 52completely separate until just after the moment of dispensing. A pair ofreceptacles 80 (only one being visible in this view) are provided toattach dual syringe body 26 to manifold 30 by receiving latches 66.Optionally, the kit 20 may include a static mixer and/or dispensing tipthat is adapted to be fitted onto nozzle 78.

[0078] Referring now to FIG. 2, a side view of the base 57 of the dualsyringe body 26 is illustrated in isolation. It will be noted that thelatches 66 each have a projection 82 which allows them to interact withthe receptacles 80 as discussed above. Referring now to FIG. 3, a bottomview of the base 57 of FIG. 2 is illustrated. In this view it can beseen that cylinders 58 and 60 have internal through bores 84 and 86respectively which are sized to receive first and second carpules 22 and24 (shown in FIGS. 1A-1D). It can also be seen that projecting inwardsfrom the walls of each of the cylinders 58 and 60 are four taperedledges 88 which interact with ridges 42 and 56 of first and secondcarpules 22 and 24 respectively to retain the carpules within the bores84 and 86.

[0079] Referring now to FIG. 4, a cross-sectional view of base 57 takenalong section lines 4-4 in FIG. 3 is illustrated. In this view it can beseen that projecting inwards from the walls of each of the cylinders 58and 60 are four tapered retainers 90 which interact with and retain dualpiston 62 within the bores 84 and 86. This will be discussed in moreparticularity below. In FIG. 5, a cross-section view of base 57 takenalong section lines 5-5 in FIG. 3 is illustrated so that the features ofthe base can be more readily seen.

[0080] Referring now to FIGS. 6 and 7, views of dual piston 62 areillustrated. A pair of push rods 92 and 94 extend from a thumb plate 96.Each of the push rods 92 and 94 has a circumferential ridge 97 and 98adapted to interact with the tapered retainers 90 discussed inconnection with FIGS. 4 and 5 to retain dual piston 62 within bores 84and 86. The free ends 100 and 102 are intended to contact movable plugs38 and 50 (seen in , FIGS. 1A-1D) to advance them and pressurize thefluid in carpules 22 and 24 when pressure is exerted by the hand of thepractitioner on the thumb plate 96.

[0081] Referring now to FIG. 8, a side view of the manifold 30 isillustrated in isolation. The manifold 30 includes barrels 104 and 106which are sized and shaped to enclose the ends of the of carpules 22 and24 having septums 32 and 44 when the carpules have been inserted intothe base 57 and the manifold has been attached to the base byinterlocking latches 66 with receptacles 80.

[0082] Referring now to FIG. 9, a bottom view of manifold 30 of FIG. 8is illustrated. In this view it can be seen that nozzle 78 includesopenings 108 and 110 to allow the components in carpules 22 and 24 to bedispensed as separate solutions. A further nozzle element (not shown)could be installed over nozzle 78 to contain and promote mixing of thetwo streams of liquid emerging from openings 108 and 110.

[0083] Referring now to FIG. 10, a cross-sectional view taken alongsection lines 10-10 in FIG. 9 is illustrated. It can now be seen thatbarrels 104 and 106 have cylindrical, hollow interiors (or cavities) 112and 114 respectively to receive the carpules 22 and 24. A pair ofpiercers 116 and 118 are provided to pierce the septums 32 and 44 whenthe manifold 30 is mounted on the base 57. The piercers are convenientlymounted on mounting disks 120 and 122, the edges of which form a sealwith the walls of cylinders 104 and 106. This may be convenientlyaccomplished by solvent bonding, by ultrasonic welding, or by having anelastomeric member (e.g., an o-ring within a groove) along the edge ofthe mounting disks 120 and 122 which contact the walls 104 and 106 andhold the mounting disks 120 and 122 in place by friction fit. Access isavailable for the contents of carpules 22 and 24 through the hollowcentral bore of each of the piercers into plenums 124 and 126 and oninto passageways (or conduits) 128 and 130 to openings 108 and 110.Several standoffs 132 are conveniently molded into the base of cavities112 and 114 to position the mounting disks 120 and 122 in the rightlocation to provide for plenums 124 and 126.

[0084] The dispenser kit is easily sterilized. In one embodiment, thecarpules can be sterile filled or e-beam sterilized, and the assembledkit undergoes a terminal sterilization (e.g., with ethylene oxide gas orgamma or e-beam irradiation).

[0085] Referring now to FIG. 11, a perspective view of an alternateembodiment of several of the elements of a dispenser 20A according tothe present invention is illustrated. The dispenser 20A includes firstcontainer 22A and second container 24A with movable plugs 38A and 50A;housing 30A and a dual syringe body 26A. The dual syringe body 26A issized and shaped to receive and support the containers 22A and 24A.

[0086] The housing 30A includes a manifold. Latches 66A (only one beingvisible in FIG. 11) are provided to attach dual syringe body 26A tohousing 30A. The latches 66A are preferably located at the proximal endof the dual syringe body 26A. The latches 66A preferably includeprojections 82A that are still sized and shaped to be received inreceptacles 80A in the housing 30A so as to snap-connect the housing 30Ato the dual syringe body 26A.

[0087] Optionally, the containers 22A and 24A (preferably carpules),dual syringe body 26A and piston 62A may be brought together into apreassembly P as shown in FIG. 11. The preassembly P makes the task ofinsertion of the containers 22A and 24A into the housing 30A moreconvenient as a user can accomplish this by simply sliding thepreassembly into the housing.

[0088] Alternatively, the latches 66A, projections and receptacles 80Amay be sized and shaped so that preassembly P may be easily, manuallyremoved from the housing 30A. The latches 66A, projections andreceptacles 80A are designed so that the preassembly P may be manuallyreleasable. In some surgical procedures, it may be desirable to replacespent carpules with new carpules. With the embodiment described withreleasable latches, it can be seen that at least portions of thedispenser 20A may be reused. This can be especially suitable in surgicalprocedures that require multiple sets of carpules to deliver the tissueadhesive or sealant. Preferably, the dispenser according to the presentinvention is only reusable on the same patient. After the surgicalprocedure on the patient, the dispenser is discarded.

[0089] Finger flange 64A is provided on the housing 30A to allow thepractitioner to grip the dispenser in the conventional manner. Fingersprings 140 and 142 engage the shoulders of the carpules 22A and 24A toretain first and second carpules 22A and 24A within the dual syringebody 26A. A limiting shoulder 146 interengages with the proximal end Eto limit the extent to which the syringe body 26A may be inserted intothe housing 30A. The element that includes limiting shoulder 146 mayhave a hole that is sized and shaped to engage legs 92A and 94A of dualpiston 62A to retain the association of the dual piston 62A with theinner portions of the carpules 22A and 24A. As a result, the taperedretainers 90 of the embodiment shown in FIG. 3 are not needed in thisembodiment.

[0090] The preassembly P is readily manufacturable as the constructionof the finger springs 142 and 144 is less sensitive to tolerances thanthe design shown in FIGS. 1-10.

[0091] The dispenser 20A may optionally include a separate dispensingtip 150 that is sized and shaped to be fitted onto nozzle 78A. Thedispensing tip 150 preferably includes a base flange 152 that is adaptedto engage complementary grips 154 and 156 adjacent the nozzle 78A. In apreferred embodiment, the dispensing tip 150 has a static mixing elementwithin its barrel 158, although this is not shown in FIG. 12.Preferably, the dispensing tip 150 includes a fluidic element 160 at thetip to provide a final mixing of the two liquid components just beforedispensing. Preferably, the orifice of the dispensing tip isapproximately circular and between about 0.005 inches to 0.010 inches(0.012 to 0.025 mm) in diameter and about 0.003 inches (about 0.0762 mm)in length. A length to diameter of the orifice of no more than 1:2 ispreferred.

[0092] Referring now to FIG. 12, a cross-section front view of theassembled embodiment of FIG. 11 is illustrated. The details of themanifold are best seen in this view. The manifold includes piercers 116Aand 1 18A that are situated in protected positions. By “protectedpositions” it is meant that a user could not readily engage the sharpsurfaces of the piercers 116A and 118A. In preferred embodiments, suchcontact is very difficult and the likelihood of it happening issubstantially reduced. Preferably, the first and second septums 32A and44A do not contact the piercers 116A and 118A until the containers 22Aand 24A are substantially inside housing 30A.

[0093] Referring to FIG. 11, if the housing 30A is opaque, the housing30A may optionally include viewing windows or slots. The viewing windows93 may be especially desirable if the housing 30A is constructed from amaterial that is opaque or if the housing is otherwise difficult to seethrough. The windows 93 allow the user to view the remaining portions ofthe tissue adhesive and/or sealant in the containers 22A and 24A. Thewindows 93 are preferably thin and elongate so as to substantiallyreduce that chance that the user will come into contact with thepiercers 116A and 118A.

[0094] The piercers 116A and 118A are mounted on mounting disks 120A and122A, the edges of each of which form a seal with the walls of cylinders104A and 106A by means of O-rings 162 and 164. Mounting disks 120A and122A are situated against standoffs 132A to create plenums 124A and126A. The first and second components of the tissue sealant or adhesivemay flow through passageways or conduits 128A and 130A. Once thecomponents of the tissue sealant or adhesive exit the passageways 128Aand 130A, they can then begin mixing in the dispensing tip 150. Thedispensing tip 150 may be made in accordance with the teachings ofAtomization and Sprays, by Arthur H. Lefebvre (published by HemispherePublishing Corporation, U.S.A. 1989) (the entire contents of which areherein incorporated by reference with specific reference to pages112-121). Preferably, a static mixer within dispensing tip 150 isconstructed to afford mixing of the first and second components of thetissue sealant or adhesive. For example, the static mixer may comprise astatic mixer similar to the static mixers taught in U.S. Pat. Nos.5,080,493 and 5,386,928 (the entire contents of which are hereinincorporated by reference).

[0095] Flange 64A is provided to allow the practitioner to grip thehousing 30A during injection in the conventional manner for syringes.The finger flange 64A is sized and shaped to afford convenient manualgrasping.

[0096] Referring now to FIGS. 13 and 14, a perspective exploded view andan assembled view of an additional alternate embodiment are illustrated.The dispenser 20B includes a housing 30B with a manifold, containers 22Band 24B, and dispensing tip 150B. The dispenser 20B is particularlysuitable for simultaneously dispensing first and second components of atissue sealant, such as, for example, the tissue sealant and/or adhesivedisclosed in U.S. Pat. No. 5,583,114 to Barrows et al. Preferably, atleast the first component is initially stored and/or shipped in thedispenser as dry powder. For example, the first component may initiallycomprise 130 mg Poly (ethylene glycol) di-succinimidyl succinate(PEGSS2) in powder form that is designed to be dissolved just prior touse by introduction of a solvent (e.g. about 1 ml of sterile water).Alternatively, for medical procedures that require additional amounts oftissue sealant, the first component may comprise 260 mg of PEGSS2 inpowder form that is designed to be dissolved just prior to use by about2 ml of sterile water.

[0097] The dispenser 20B comprises a first container 22B having a firstseptum 32B at one end, an open end 36B opposite the first septum, and afirst movable plug 38B disposed therein. The first container 22Binitially contains a quantity of the first component in the form of adry powder stored between the first septum 32B and the first movableplug 38B. The first component is preferably stored and/or shipped in adry powder/separate solvent solution until just prior to use of thedispenser 20B to deliver or apply a tissue sealant and/or adhesive to apatient. Just prior to use of the dispenser 20B to deliver or apply atissue sealant and/or adhesive to a patient, the dry powder may bedissolved in a solvent. FIG. 14 illustrates the container 22B after thesolvent has been added and air has been expunged.

[0098] The dispenser 20B includes a second container 24B comprising asecond septum 44B at one end, an open end 48B opposite the second septum44B, and a second movable plug 50B disposed therein. The secondcontainer 24B contains a quantity of the second component, preferably inliquid form (e.g. 1 mL Human Serum Albumin solution). Preferably, thesecond component is stored and shipped in this liquid form.

[0099] The dispenser 20B includes housing 30B having internal surfaceswith first and second piercers 116B and 118B that are preferably sharpto pierce the first and second septums of the first and secondcontainers 22B and 24B. The first and second piercers 116B and 118B aresituated in protected positions so that the first and second septums maybe pierced without exposing a user to contact with the first or secondpiercers 116B and 118B. The housing 30B affords passage of the first andsecond components via first and second flow paths to a nozzle 78B fromwhich the first and second components are dispensed to combine to formthe adhesive tissue sealant.

[0100] Pistons are sized and configured to be received in the open ends36B and 48B of the first and second containers 22B and 24B to advancethe first and second movable plugs 38B and 50B. Preferably, the pistonsare provided by dual piston 62B.

[0101] A manually removable dual body in the form of retainer 129 issized and shaped to receive the containers 22B and 24B. The retainer 129protects and supports the containers 22B and 24B. The retainer 129 isparticularly suitable when the containers 22B and 24B are constructedfrom glass that may be broken.

[0102] The retainer 129 may engage the proximal end of the housing 30B.Preferably the retainer 129 includes attachment means for releasablyengaging the housing 30B. In a preferred embodiment, the attachmentmeans are manually releasable and may reattach the retainer 129 to thehousing 30B. The retainer 129 may, for example, be held onto the housing30B by a press fit, or conveniently have an extending arm 127 whichlatches over a lip 166 near the proximal end of the housing 30B.

[0103] As best seen in FIG. 14, the retainer 129 preferably includes adistal end 121 and a proximal end 123 having an opening. The containers22B and 24B are received in the opening of the retainer 129. Thecontainers 22B and 24B can be easily slid through the retainer 129 sothat the septums 32B and 44B may be pierced by piercers 116B and 118B.Also preferably, the retainer 129 is sized and shaped so that the openends 36B and 48B of the first and second containers 22B and 24B do notproject substantially beyond the opening of the retainer.

[0104] It may sometimes be desirable to reuse the same housing 30Bduring a surgical procedure on a single patient. This may beaccomplished by loading new containers 22B and 24B in the housing 30Band optionally changing the dispensing tip 150B. In such a procedure, itis desireable to replace each container 22B and 24B with a container ofthe same substance so there will not be inadvertant premature reactionsof components within the piercers 116B and 118B or plenums 124B and126B. One way of helping insure that this occurs is to provide anindexing means (e.g. color code) the carpules 22B and 24B, convenientlyby color anodizing the metal caps that retain the septums. These thencan be matched up with an indexing means such as a color code on theretainer 129 and/or the housing 30B. When this is done, it is desirableto provide a specific orientation for the retainer 129 on the housing30B. One way in which the can be conveniently accomplished is to placean optional indexing projection 168 on the housing 30B and a matchingkeyway 170 on the retainer 129. Alternatively, the replacementcontainers 22B and 24B and new body 129 may be packaged separately toprovide a replacement subassembly.

[0105] Referring again to FIG. 14, a cross-section front view of theassembled alternate embodiment of FIG. 13 is illustrated. Optionalstatic mixer 170 and an optional seal 172 are included within thedispensing tip 150B. The seal 172, when present, serves to keep thecomponents of the tissue adhesive and/or sealant separated until thestatic mixing zone.

[0106] The portion of the tip 150B that includes the opening 160B isconveniently fabricated by injection molding of a polymer, withpolycarbonate resin considered suitable. For example, the USP Class VIgrade polycarbonate commercially available as RX2530-118 from Bayer maybe used. The seal element 172 may be molded from a medical gradesilicone rubber. The remaining portions of the dispensing tip 150B maybe molded from medical grade polypropylene.

[0107]FIG. 15 illustrates one example of a kit 20C according to thepresent invention. The kit includes elements useful for preparing anddelivering a two component tissue sealant and/or adhesive just prior touse, such as the tissue adhesive/sealant described above with referenceto FIGS. 13 and 14.

[0108] The kit comprises first container 22C having a septum 32C and atleast a portion of a first component of the tissue sealant and/oradhesive (e.g. a dry powder) stored therein, and outer portions thathave preferably been sterilized, a second container 24C having at leasta portion of the second component (e.g. in the form of a liquid) storedtherein and a septum 44C, and outer portions that have preferably beensterilized. When the second component of the tissue adhesive and/orsealant is provided in liquid form, the kit may be free of any solutionfor reconstituting the second component within the second container 24C.

[0109] The kit preferably includes a vial 174 (with inner and outerportions preferably sterile) with a solvent for the dry powder therein.The kit also includes syringe and needle 28C (preferably sterile). Thekit also includes dispenser capable of dispensing the tissue sealantand/or adhesive. As best seen in FIG. 14, the dispenser has first andsecond piercers 116B and 118B located in protected positions and aportion that is sized and shaped to receive the first and secondcontainers.

[0110] The components of the kit 20C are packaged within a first package187. Preferably the inside and outside portions of the elements of thekit 20C are provide in a sterile condition. More preferably, the firstpackage 187 is packaged within a second package 189 and the componentswithin the second package 189 are provided in a sterile condition.

[0111] The kit optionally includes one or more dispensing tips 150C anddual piston 62C.

[0112]FIGS. 18 through 26 illustrate the use of the kit 20C to deliver atissue adhesive and/or sealant. If the kit 20C is used to prepare anddeliver a tissue adhesive and/or adhesive disclosed in U.S. Pat. No.5,583,114, then the first and second components may be dispensed withoutbeing heated above room temperature. This removes any need to use thekit 20C in conjunction with heating and/or stirring instrumentation.This further simplifies the use of the kit 20C to prepare and deliver atissue adhesive and/or sealant.

[0113] Preferably, the first and second containers 22C and 24C, thedispenser (e.g. 30C), the vial 174 and syringe and needle 28C areprovided in sterile condition within first package 187 and the firstpackage 187 is provided in a sterile fashion within a second package189. In this fashion, the second package 189 may be opened by ahealthcare worker outside a sterile area (e.g. a circulating nurse) andthe first package 187 may be aseptically taken from the second package189 and placed in the sterile area by a healthcare worker associatedwith the sterile area (e.g. a scrub nurse). The first and secondpackages 187 and 189 may comprise bags (e.g. pouches) or trays orcombinations thereof. Trays offer an advantage in that they reduce thenumber of separate, individual waste products associated with the kit.If the packages 187 or 189 comprise a bag, they are preferablyconstructed from suitable materials capable of withstandingsterilization processes. For example, such materials include TYVEKand/or MYLAR.

[0114]FIG. 18 illustrates the syringe 28C being used to remove thesolvent from solvent container 174. The syringe 28C loaded with solventmay then be used to pierce the septum 32C of the container 22C and toinject the solvent for the first component into container 22C.Preferably, the steps shown in FIGS. 18 and 19 are conducted by a singlehealthcare worker (e.g. a scrub nurse). This removes any need for onehealthcare worker to coordinate with another healthcare worker in orderto reconstitute any of the components of the tissue adhesive and/orsealant. Alternatively, the solvent may be stored within syringe 28C asthe kit is provided (as described above), or the solvent may be storedwithin the storage bottle 174. This may have the advantage of making thetask of sterilizing the total kit for surgical use more convenient.

[0115] As shown in FIG. 20, the first container 22C is preferablyagitated briefly to speed the process of dissolving the first component(e.g. a dry powder) in the solvent. Both containers 22C and 24C may thenbe inserted though holes in the retainer 129 and impaled on piercers116B and 118B in the manner shown in FIG. 21. This can be readilyconducted by a single healthcare worker without unduly exposing thehealthcare worker to the piercers or requiring the healthcare worker tocoordinate with another healthcare worker.

[0116] As shown in FIG. 22, dual plunger 62C is inserted into theretainer 129 and on into the distal ends of containers 22C and 24C,lightly touching movable plugs. Spring legs 176 on the dual plunger 62Cmay conveniently be placed on push rods 92C and 94C to provide a slightfriction between the dual plunger 62C and the containers 22C and 24C soas to retain the dual plunger before use.

[0117] After the syringe 28C adds solution to the container 22C (seeFIG. 19), some air remains in the container. As shown in FIG. 23, air ispreferably expressed from the assembly. Preferably, after the syringeadds the solution to the powder, the movable member 38B (see FIG. 14 forthe member 38B, not its position) is slightly axially offset relative tothe movable member 50B so that the dual plunger 62B initially moves themovable member 38B to express the air without moving the movable member50B. FIG. 14 illustrates the movable members 38B and 50B after the airhas been expressed from the first container so that the movable membersare substantially axially aligned. In FIG. 24, the distal end (nozzle)of the housing 30C is preferably wiped clean to provide a clean surfacefor receiving the dispensing tip 150C.

[0118] Optionally, but preferably, at least one dispensing tip 150C willbe provided, and in some preferred embodiments a second tip will beprovided. Placement of the dispensing tip 150C on the housing 30C isshown in FIG. 25. If only a portion of the contents of the containers22C and 24C is dispensed, and then enough time passes that the mixturewithin the dispensing tip 150C cross-links or cures sufficient to clogdispensing tip 150C, the second dispensing tip can be attached so thatthe remain contents of the containers 22C and 24C can be dispensed.

[0119] The tissue adhesive and or sealant may then be dispensed orapplied as shown in FIG. 26. When the tissue sealant is a tissue sealantconstructed according to one embodiment of the teachings of U.S. Pat.No. 5,583,114, “ADHESIVE SEALANT COMPOSITION,” then the sealant ispreferable dispensed about two inches from the tissue.

[0120] In some preferred embodiments, the elements depicted areconveniently packaged together, conveniently all on a single tray formedof e.g. PET, conveniently covered with a cover of e.g. TYVEK spun-bondedpolyolefin heat sealed to the tray. If the several elements are mostconveniently sterilized for surgical use using different sterilizingtechniques, the kit may be provided in two packages, each holding theelements that are expeditiously sterilized together.

[0121] It should be noted that all of the steps shown in FIGS. 18-25 maybe conducted by a single individual. The step of placing the solvent inthe first container (FIG. 18) and the steps of installing the first andsecond containers in the dispenser (FIG. 22) and piercing the septums ofthe first and second containers (also FIG. 22) with the first and secondpiercers are especially convenient when conducted by a single healthcareworker as one healthcare worker need not coordinate activities withanother healthcare worker.

[0122]FIGS. 16 and 17 illustrate another embodiment of kit according tothe present invention. In FIG. 16, the first and second containers 22Cand 24C may be provided in a separate minor subassembly kit 200.Alternatively, the entire preassembly P (See FIG. 11) may be provided ina minor subassembly kit.

[0123]FIG. 17 illustrates a major subassembly kit 220 that includeshousing 30D, piston 62D, dispensing tips 150D, syringe and needleassembly 28D and solvent (e.g. water) bottle 174D.

[0124] The minor subassembly kit 200 may include those elements of thetissue adhesive and/or sealant that include a relatively short shelflife. For example, such labile elements may include a protein solution(e.g. albumin) and dry powder cross-linker component. In another aspectof the present invention, the minor subassembly kit 200 may includethose elements of the tissue sealant and/or adhesive that require adifferent temperature range for storage than the components of the majorsubassembly kit 220. For example, the minor subassembly kit may includethose items that require refrigeration until just prior to use.

[0125] In yet another aspect of the invention, the minor subassembly mayinclude those elements of the tissue adhesive and or sealant dispenserthat are packaged for a sterilization technique that is different thanother portions of the tissue adhesive and or sealant dispenser. Forexample, the dry powder and liquid components of an adhesive tissuesealant may be sterilized within containers using a low dose e-beamtechnique (e.g. about 10-20 kGy) and then terminally sterilized using anethylene oxide sterilization technique. However, the remaining portionsof the dispenser need only be subjected to an ethylene oxidesterilization technique. In this embodiment, if the major subassemblyincludes all of the elements of the kit except containers 22C and 24C,then a majority of the elements of the kit can be sterilized withoutsubjecting them to the effects of the e-beam sterilization technique.

[0126] Other embodiments of the invention are within the scope of thefollowing claims. E.g., in some aspects of the invention, materialsother than an adhesive tissue sealant may be dispensed, or the solventfor dissolving the dry powder could be nonaqueous. More than two barrelsand carpules (e.g., three) could be fitted to a syringe body andmanifold. Individual pistons could be used instead of the dual piston. Akit may be sterilized as a whole (e.g. using e-beam or gammasterilization techniques). Alternatively, individual components may besterilized, the kit assembled, and then a terminal sterilization of theentire kit could occur.

What is claimed is:
 1. A method for dispensing a first component of anadhesive tissue sealant stored in the dispenser as dry powder that isdissolved prior to use by introduction of a solvent, the methodcomprising: (a) providing a first carpule comprising a first septum atone end, an open end opposite the first septum, and a first movable plugdisposed therein, the first carpule containing the dry powder storedbetween the first septum and the first movable plug; (b) introducing thesolvent into the first carpule to dissolve the dry powder to form asolution of the first component by piercing the first septum with asyringe and injecting the solvent into the first carpule; (c) installingthe first carpule in a housing having a piercer; (d) placing a pistonwithin the open end of the carpule to contact and advance the firstmovable plug; and (e) piercing the first septum with the piercer of thehousing to afford passage of the solution of the first component via aflow path to a nozzle from which the first component is dispensed. 2.The method of claim 1 wherein step (b) is performed before step (c). 3.The method of claim 1 wherein, prior to use, the first movable plug ispositioned in a position in which the space between the plug and theseptum is substantially the minimum necessary to contain the dry powder,thereby reducing the amount of air in that space and reducing thepressure increase within the carpule when the solvent is introduced bypiercing the first septum.
 4. The method of claim 1 further comprisingthe step of providing a second carpule comprising a second septum at oneend, an open end opposite the second septum, and a second movable plugdisposed therein, the second carpule containing a second component, andwherein the housing is sized and configured to accept the first andsecond carpule.
 5. The method of claim 4 wherein the second component isa protein in an aqueous buffer and is capable of reacting with the firstcomponent to provide an adhesive tissue sealant.
 6. The method of claim5 wherein the dry powder of the first component comprises awater-compatible or water-soluble cross-linking agent capable ofreacting with the second component to provide the adhesive tissuesealant.
 7. A method of preparing a multiple component tissue sealantand/or adhesive just prior to use comprising the steps of: providing afirst container having a septum and a dry powder stored therein;providing a second container having a septum and a liquid therein;providing a vial with a solvent for the dry powder therein; providing asyringe and needle; providing a housing having first and second piercerslocated in protected positions and a portion that is sized and shaped toreceive the first and second containers; withdrawing the solvent fromthe vial with the syringe and needle; placing the solvent in the firstcontainer; and installing the first and second containers in the housingand piercing the septums of the first and second containers with thefirst and second piercers without exposing a user to physical contactwith the piercers.
 8. A method according to claim 7 wherein the firstand second components may be dispensed without being heated above roomtemperature.
 9. A method according to claim 7 where the step ofproviding a syringe and needle comprises the step of providing a singlesyringe and a single needle for the syringe.
 10. A method according toclaim 7 wherein the first and second containers, the dispenser, the vialand syringe and needle are provided in sterile condition so that thetissue adhesive and/or sealant may be prepared by a single healthcareworker associated with a sterile field without the need to coordinatewith another healthcare worker outside the sterile field.
 11. A methodaccording to claim 7 wherein the multiple component tissue sealantand/or adhesive comprises a two component tissue sealant and/oradhesive; and the second component is provided as the liquid in thesecond container without requiring reconstitution of the secondcomponent just prior to use of the tissue sealant and/or adhesive.
 12. Amethod according to claim 7 wherein the step of placing the solvent inthe first container and the steps of installing the first and secondcontainers in the housing and piercing the septums of the first andsecond containers with the first and second piercers are conducted by asingle healthcare worker.
 13. A method according to claim 7 furthercomprising the step of providing a dispensing tip that is attachable tothe housing.
 14. A method according to claim 7 wherein the first andsecond containers, the dispenser, the vial and syringe and needle areprovided in sterile condition within a first package and the firstpackage is provided in a sterile condition within a second package sothat the second package may be opened by a healthcare worker outside asterile field and the first package may be aseptically taken from thesecond package and placed in the sterile field by a healthcare workerassociated with the sterile field.
 15. A kit having components usefulfor preparing and delivering a tissue sealant and/or adhesive havingfirst and second components, the kit comprising: a first containerhaving a septum, at least a portion of the first component storedtherein, and outer portions; a second container having at least aportion of the second component therein, a septum, and outer portions; avial with a solvent for at least one of the first and second componentstherein; a syringe and needle; and a sterile housing having first andsecond piercers located in protected positions and a portion that issized and shaped to receive the first and second containers.
 16. A kitaccording to claim 15 wherein the kit comprises a single syringe and asingle needle.
 17. A kit according to claim 15 wherein the kit is freeof any solution for reconstituting the second component within thesecond container.
 18. A kit according to claim 15 wherein the componentsof the kit are packaged within a first package and the first package ispackaged within a second package and the components within the secondpackage are provided in a sterile condition.
 19. A kit according toclaim 15 wherein the outer portions of the first and second containersare provided in a sterile condition.
 20. A kit according to claim 15wherein the portion of the first component stored in the first containeris a dry powder, and the vial includes a solvent for the dry powder. 21.A kit according to claim 15 wherein the portion of the second componentin the second container comprises the second component in the form of aliquid.